Nck2

Nck2, also known as NCK adaptor protein 2, is a cytoplasmic signaling protein in humans encoded by the NCK2 gene. It is one of the two vertebrate Nck family adaptor proteins, Nck1 and Nck2, which function as non-enzymatic links between receptor tyrosine kinases and downstream effectors that regulate the actin cytoskeleton. Nck2 participates in transducing signals from activated receptors to actin remodeling pathways and other cytoskeletal rearrangements.

Nck2 has a modular structure comprising an N-terminal SH2 domain followed by three SH3 domains. The SH2 domain binds phosphotyrosine-containing motifs on activated receptor tyrosine kinases or adaptor proteins, whereas the SH3 domains bind proline-rich regions in downstream effectors. Through these interactions, Nck2 serves as a scaffold that assembles signaling complexes needed for cytoskeletal dynamics.

In signaling pathways, Nck2 links diverse receptors to actin-regulatory proteins such as N-WASP and p21-activated kinases, promoting Arp2/3-mediated actin polymerization and changes in cell shape and motility. It participates in signaling downstream of receptor tyrosine kinases including EGFR, PDGFR, and FGFR, and can influence processes such as cell migration, neurite outgrowth, and growth cone navigation. Nck2 often functions redundantly with Nck1, and both adaptors contribute to proper development and cellular responses to external cues.

Nck2 is expressed in multiple tissues with variable levels and can generate multiple isoforms through alternative splicing. Altered NCK2 expression or function has been examined in the context of cancer cell motility and metastasis, reflecting its role in cytoskeletal organization and signaling.